This is a proposal to study the maturation of T lymphocyte progenitors in the bone marrow and thymus of mice. An in vitro technique for growing these progenitors to produce colonies (the CFU-pre-T assay) will be used to investigate the nature of progenitors, their changes with age, and their dependence upon a humoral factor or thymic hormone. The hormone which causes the proliferation and maturation of CFU-pre-T will be purified and characterized. The site where the generation of diversity takes place in developing T cells -bone marrow or thymus - will be determined by in vitro and in vivo clonal abortion experiments, and the number of clones in a normal thymus measured using X-linked enzyme variants. The nature of the interaction between developing thymocytes and epithelial "nurse" cells will be investigated, to see if this has a central role in the generation of major histocompatibility complex restriction.